Cyclooxygenase 2 (COX2)‎ and Peroxisome Proliferator-Activated Receptor Gamma (PPARG)‎ Are Stage-Dependent Prognostic Markers of Malignant Melanoma

Abstract EN

Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM).

TMA-1 contained normal and tumor tissues (n=3448) from 47 organs including skin neoplasms (n=323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi.

Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3.

COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival.

Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival.

Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence.

In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.